CN111603298B - Preparation process method of transient medical chip - Google Patents
Preparation process method of transient medical chip Download PDFInfo
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- CN111603298B CN111603298B CN202010426778.4A CN202010426778A CN111603298B CN 111603298 B CN111603298 B CN 111603298B CN 202010426778 A CN202010426778 A CN 202010426778A CN 111603298 B CN111603298 B CN 111603298B
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Abstract
The invention discloses a preparation process method of a transient medical chip, belonging to the technical field of novel microelectronic materials and devices, biodegradable electronic devices and medical electronic devices. The medical chip of the method constructs a three-dimensional stacked multifunctional transient medical chip, and the multifunctional medical chip is characterized by mainly comprising the following steps: 1) is formed by stacking two or more layers of devices; 2) different pairs of stacked devices have the same or different medical functions; 3) the materials required for preparing the device are all made of biodegradable electronic materials; 4) different biodegradable insulating materials are used for packaging different device layers. The invention can accelerate the rapid development of novel medical electronic devices, and has profound significance in the aspects of improving the multifunctional integration of transient medical electronic devices, reducing the medical cost of patients and the like.
Description
Technical Field
The invention discloses a preparation process method of a transient medical chip, belonging to the technical field of novel microelectronic materials and devices, biodegradable electronic devices and medical electronic devices.
Background
Transient medical electronics have been proposed to the present (Science,2012,337,1640.) since 2012, and have been widely noticed and developed due to a series of advantages of biocompatibility, biodegradability, no environmental pollution, etc. Particularly with respect to implantable electronic devices, transient medical electronic devices can degrade themselves within a living body after they have completed treatment or monitoring of the living body, without the need for a second surgical procedure to remove them. The presentation and the application of the transient medical electronic device can greatly reduce the operation pain and the operation risk of patients and simultaneously reduce the medical cost. The key to realizing the transient medical electronic device is that the materials needed from the substrate, the device to the packaging layer have the characteristics of biocompatibility and biodegradability at the same time. However, the lifetime of the conventional transient medical electronic device in a living body is determined by the degradation rate of the encapsulation layer, and has the disadvantages of single function, low integration level, and the like. For example, implantable transient hyperthermia devices with infection reduction or elimination are not known for their efficacy in the affected area when they are completely degraded in vivo.
Three-dimensional integration of the treatment device with the monitoring device is an effective way. For example, the treatment device is located on the upper layer, the monitoring device is located right below the treatment device, the two layers of devices are isolated by the packaging layer, and the upper part of the treatment device layer is packaged. When the treatment device is fully degraded, the monitoring device below the treatment device can carry out in-situ monitoring on the curative effect of the treatment device. By monitoring the feedback of data, the lifetime of the therapeutic device within the living body is optimized, i.e. the uppermost encapsulation layer is optimized. Thus, when the treatment device is completely degraded, the diseased region is completely recovered as usual, and the recovery condition can be analyzed in situ by the monitoring device below. The invention further promotes the development of the transient medical electronic device, and has important significance for greatly expanding the medical and practical application of the transient medical electronic device. In view of this, it becomes necessary to construct a three-dimensional stacked multifunctional transient medical chip.
Disclosure of Invention
According to the technical background, the invention aims to construct a three-dimensional stacked multifunctional transient medical chip, and the medical chip with multifunctional integration, transient and three-dimensional stacking is finally formed by longitudinally stacking device layers with the same or different functions in three positions and using an insulating medium as a package between the device layers. The three-dimensional stacked multifunctional transient medical chip provided by the invention has important significance for promoting the rapid development of the transient medical electronic device and expanding the medical and practical application of the transient medical electronic device.
In order to achieve the above and other related objects, the present invention provides a method for manufacturing a transient medical chip in a three-dimensional stacking manner, which at least comprises the following steps:
1) coating a biodegradable substrate precursor on a temporary substrate by a spin coating method or a titration method;
2) constructing a monitoring device layer on the biodegradable substrate for in-situ monitoring of the therapeutic effect of the therapeutic device;
3) constructing a first packaging layer on the monitoring device layer;
4) constructing a therapeutic device on the first encapsulation layer for accelerating healing of the infected wound;
5) constructing a second encapsulation layer on the therapeutic device for preventing the tissue fluid from rapidly degrading the therapeutic device;
6) stripping the constructed stacked multifunctional transient medical chip from the temporary substrate;
7) and tightly attaching the constructed flexible stacked multifunctional transient medical chip to the diseased organ.
Optionally, the biodegradable substrate is made of a biocompatible, biodegradable material, and has flexible characteristics; the functional device layer is made of biocompatible and biodegradable materials; the packaging layer is made of a biocompatible and biodegradable material; the functional device layer and the encapsulation layer are repeatedly stacked one or more times, wherein different device layers have the same or different medical functions.
Optionally, the biocompatible and degradable substrate material mainly includes, but is not limited to, fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL), polyglycolic acid (PGA), and the like.
Optionally, the metal material required by the functional device layer includes Zn, Mg, Fe, W, Mo, the dielectric material is SiO2, Si3N4, MgO, degradable polymer, and the semiconductor material is Si, Ge, SiGe, ZnO, but is not limited to the above.
Optionally, the biodegradable electronic device layer includes a single element such as a transistor, a memristor, a diode, a resistor, an inductor, a capacitor, or an integrated system composed of the above elements.
Optionally, the encapsulation layer comprises inorganic SiO2、Si3N4MgO, or organic fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL), polyglycolic acid (PGA), and the like, but are not limited thereto.
As described above, the present invention provides a three-dimensional stacked multifunctional transient medical chip. The invention has the following advantages and prominent technical effects: 1) different from the traditional medical electronic device with single medical function, the multifunctional transient medical chip provided by the invention integrates the specific functions of different device layers on the same chip, thereby greatly increasing the integration level of the chip; 2) the specific medical functions among different device layers on the multifunctional transient medical chip have the characteristic of mutual synergistic action, so that the working efficiency of a single chip is improved; 3) the multifunctional transient medical chip provided by the invention can be used for carrying out in-situ monitoring on the curative effect of each device layer, and has important guiding significance for analyzing the illness state of a patient, the curative effect of a medical device and the like; 4) the multifunctional transient medical chip provided by the invention is completely composed of biocompatible and biodegradable materials, can be automatically degraded without secondary operation after being placed into a living body, greatly relieves the pain of patients, and reduces the operation risk and medical cost.
Drawings
Fig. 1 shows a method for preparing a biodegradable, biocompatible substrate in a three-dimensional stacked multifunctional transient medical chip according to the present invention.
Fig. 2 shows the preparation of a monitoring device and a packaging layer 1 in a three-dimensional stacked multifunctional transient medical chip according to the present invention.
Fig. 3 shows the preparation of the therapeutic device and the packaging layer 2 in the three-dimensional stacked multifunctional transient medical chip of the invention.
Fig. 4 shows the multifunctional transient medical chip being peeled off from the temporary substrate in a three-dimensional stacked multifunctional transient medical chip according to the present invention.
Fig. 5 shows a three-dimensional stacked multifunctional transient medical chip according to the present invention, in which the multifunctional transient medical chip is closely attached to a diseased organ.
Figure 6 shows a combination of functional layers and encapsulation layers according to the present invention.
Detailed Description
The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.
It should be noted that the present embodiment provides only one specific step for preparing the multifunctional transient medical chip to illustrate the basic concept of the present invention, and only the relevant contents related to the present embodiment are shown in the step. In practical implementation of the present invention, the function of the device layer with required function and the number of stacked layers can be changed as required to realize the required medical function, and the material and thickness of the encapsulation layer can be changed to control the degradation rate of the functional device layer, and the layout of the components may be more complicated.
As shown in fig. 1-6, a three-dimensional stacked multifunctional transient medical chip at least comprises: the device comprises a substrate, a functional device layer and an encapsulation layer;
1) providing a biocompatible, biodegradable material as a substrate, the biocompatible/degradable substrate having flexible characteristics; 2) constructing a first functional device layer on the biocompatible/degradable substrate, wherein the materials required by the functional device layer are all biocompatible and biodegradable materials; 3) encapsulating the functional device layer, wherein materials required by the encapsulating layer are all biocompatible and biodegradable materials; 4) The functional device layer and the encapsulation layer are repeatedly stacked one or more times, wherein different device layers have the same or different medical functions.
Optionally, the biocompatible and degradable substrate material mainly comprises fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL), and polyglycolic acid (PGA).
Optionally, the preparation method of the biocompatible and degradable substrate comprises a spin coating method or a titration method, and the thickness of the finally obtained substrate is 1-500 m.
Optionally, the functional device layer includes an active device, a passive device, and a functional electronic circuit composed of the active device and the passive device.
Optionally, the metal material required by the functional device layer includes Zn, Mg, Fe, W, Mo; the dielectric material comprises SiO2、Si3N4MgO, degradable polymers; the semiconductor material comprises Si, Ge, SiGe, ZnO.
Optionally, the biodegradable electronic device layer includes a single element such as a transistor, a memristor, a diode, a resistor, an inductor, and a capacitor, or an integrated system composed of the above elements.
Optionally, the encapsulation layer includes inorganic SiO2、Si3N4MgO, or organic fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL), polyglycolic acid (PGA), and the like.
The process flow diagram of the method of the invention comprises the following steps:
1) as shown in fig. 1, the biodegradable substrate precursor is applied to the temporary substrate by spin coating or titration, in this particular case, the biodegradable substrate is PLGA obtained by titration, and the temporary substrate is a silicon wafer;
2) as shown in fig. 2, a monitoring device layer is constructed on the biodegradable substrate for in-situ monitoring of the therapeutic effect of the therapeutic device, in this particular case, the monitoring device used is a silicon-based virus sensor;
3) as shown in fig. 2, an encapsulation layer 1 is constructed on the monitoring device layer, in this specific example, the encapsulation layer 1 is a PLGA thin film obtained by a spin coating method;
4) as shown in fig. 3, a therapeutic device is constructed on the encapsulation layer 1, for accelerating the healing of an infected wound,
in this particular example, the therapeutic device constructed was a Mg-based thermotherapy device;
5) as shown in fig. 3, an encapsulation layer 2 is constructed on the therapeutic device for preventing the tissue fluid from rapidly degrading the therapeutic device, in this particular case, the encapsulation layer 2 is constructed in a silicon oxide/silicon nitride multilayer structure, so that the service life of the therapeutic device is longer than the expected healing time of the infected wound;
6) as shown in fig. 4, the constructed stacked multifunctional transient medical chip is peeled off from the temporary substrate;
7) as shown in fig. 5, the constructed flexible stacked multifunctional transient medical chip is closely attached to a diseased device, and attention is paid to: in practice, the organs of the living body should be curved surfaces, and for the sake of simplicity, the schematic diagram is replaced by a plane;
8) after the packaging layer 2 and the therapeutic device are completely degraded by tissue fluid in a living body, detecting the vital signs of the original diseased organ by using the silicon-based virus sensor, thereby monitoring the curative effect of the therapeutic device; when the monitoring work is finished, the tissue fluid can be degraded; thus, the preparation, work and degradation of the multifunctional transient medical chip are completed.
It should be noted that, for convenience in this embodiment, the biodegradable multifunctional transient medical chip takes the Mg-based hyperthermia device as a therapeutic device and the silicon-based virus sensor as a monitoring device to illustrate the idea of the present invention and the preparation method of the material and the device, but the three-dimensional stacked multifunctional transient medical chip with other functions is also within the protection scope of the present invention.
In summary, the three-dimensional stacked multifunctional transient medical chip provided by the present invention relates to the construction of two or more functional device layers, and the multifunctional medical chip is characterized by mainly comprising: 1) is formed by stacking two or more layers of devices; 2) different pairs of stacked devices have the same or different medical functions; 3) the materials required for preparing the device are all made of biodegradable electronic materials; 4) different biodegradable insulating materials are used for packaging different device layers. The invention can accelerate the rapid development of novel medical electronic devices, and has profound significance in the aspects of improving the multifunctional integration of transient medical electronic devices, reducing the medical cost of patients and the like.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (10)
1. A preparation process method of a transient medical chip adopts a three-dimensional stacking mode and is characterized in that: at least comprises the following steps:
1) coating a biodegradable substrate precursor on a temporary substrate by a spin coating method or a titration method;
2) constructing a monitoring device layer on the biodegradable substrate for in-situ monitoring of the therapeutic effect of the therapeutic device;
3) constructing a first packaging layer on the monitoring device layer;
4) constructing a therapeutic device on the first encapsulation layer for accelerating healing of the infected wound;
5) constructing a second encapsulation layer on the therapeutic device for preventing the tissue fluid from rapidly degrading the therapeutic device;
6) the constructed stacked multifunctional transient medical chip is peeled off from the temporary substrate.
2. The preparation process method according to claim 1, wherein:
1) the biodegradable substrate is made of a biocompatible and biodegradable material and has a flexible characteristic;
2) the monitoring device layer and the therapeutic device are made of biocompatible and biodegradable materials;
3) the encapsulation layer is made of biocompatible and biodegradable material.
3. The preparation process method according to claim 1, wherein: the biodegradable substrate material mainly comprises fibroin, lactic acid-glycolic acid copolymer (PLGA), rice paper (rice paper), Polycaprolactone (PCL) and polyglycolic acid (PGA).
4. The preparation process method according to claim 1, wherein: the preparation method of the biodegradable substrate comprises a spin-coating method or a titration method, and the thickness of the finally obtained substrate is 1-500 mu m.
5. The preparation process method according to claim 1, wherein: the monitoring device layer and the treatment device comprise active components, passive components and functional electronic circuits consisting of the active components and the passive components.
6. The production process method according to claim 4, wherein: the metal materials required by the monitoring device layer and the therapeutic device comprise Zn, Mg, Fe, W and Mo.
7. The production process method according to claim 4, wherein: the dielectric material comprises SiO2、Si3N4MgO, degradable polymer.
8. The production process method according to claim 4, wherein: the semiconductor material comprises Si, Ge, SiGe, ZnO.
9. The preparation process method according to claim 1, wherein: the monitor device layer comprises a single element of a transistor, a memristor, a diode, a resistor, an inductor and a capacitor, or an integrated system formed by the elements.
10. The preparation process method according to claim 1, wherein: the packaging layer comprises inorganic SiO2、Si3N4MgO, or organic fibroin, lactic-co-glycolic acid (PLGA), rice paper (rice paper), Polycaprolactone (PCL), polyglycolic acid (PGA).
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014011690A1 (en) * | 2012-07-09 | 2014-01-16 | California Institute Of Technology | Implantable vascular system biosensor with grown capillary beds and uses thereof |
| CN105496423A (en) * | 2010-03-17 | 2016-04-20 | 伊利诺伊大学评议会 | Implantable biomedical devices on bioresorbable substrates |
| CN108083223A (en) * | 2018-01-15 | 2018-05-29 | 杭州臻镭微波技术有限公司 | The radio frequency micro-system and its manufacturing method of a kind of silicon based three-dimensional Manufacturing resource |
| CN108389893A (en) * | 2011-12-01 | 2018-08-10 | 伊利诺伊大学评议会 | It is designed to undergo the transient state device of programmable transformation |
| CN108727640A (en) * | 2018-05-31 | 2018-11-02 | 中国科学院苏州纳米技术与纳米仿生研究所 | A kind of Transient Thin-Film, the preparation method of Transient Thin-Film and Transient Thin-Film device |
| CN109045063A (en) * | 2018-10-17 | 2018-12-21 | 西北大学 | A kind of injecting temperature sensitive in situ response water soluble chitosan composite hydrogel and its preparation method and application for lacrimal passage embolism |
| CN109285915A (en) * | 2018-08-08 | 2019-01-29 | 西安电子科技大学 | A kind of flexibility transient state silicon thin film phototransistor and production method |
| CN109528392A (en) * | 2018-10-19 | 2019-03-29 | 浙江大学 | A kind of intelligent antiseptic dressing for infective wound surface perception and therapeutic intervention |
| CN110604566A (en) * | 2019-09-24 | 2019-12-24 | 清华大学 | Flexible deformable degradable brain detection treatment device and system and manufacturing and using methods |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7228162B2 (en) * | 2003-01-13 | 2007-06-05 | Isense Corporation | Analyte sensor |
| US8798751B2 (en) * | 2011-06-09 | 2014-08-05 | Medtronic, Inc. | Method and apparatus to manage lead-related conditions for fault tolerance enhancements |
| WO2014138465A1 (en) * | 2013-03-08 | 2014-09-12 | The Board Of Trustees Of The University Of Illinois | Processing techniques for silicon-based transient devices |
| JP6561368B2 (en) * | 2013-04-12 | 2019-08-21 | ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティー オブ イリノイ | Materials, electronic systems, and modes for active and passive transients |
| BR112019027090A2 (en) * | 2017-06-27 | 2020-07-07 | Lts Lohmann Therapie-Systeme Ag | self-adhesive sticker |
| CN108922854B (en) * | 2018-06-14 | 2020-06-05 | 中国电子科技集团公司第二十四研究所 | Implementation method of transient circuit packaging structure for packaging silicon-based chip |
-
2020
- 2020-05-19 CN CN202010426778.4A patent/CN111603298B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105496423A (en) * | 2010-03-17 | 2016-04-20 | 伊利诺伊大学评议会 | Implantable biomedical devices on bioresorbable substrates |
| CN108389893A (en) * | 2011-12-01 | 2018-08-10 | 伊利诺伊大学评议会 | It is designed to undergo the transient state device of programmable transformation |
| WO2014011690A1 (en) * | 2012-07-09 | 2014-01-16 | California Institute Of Technology | Implantable vascular system biosensor with grown capillary beds and uses thereof |
| CN108083223A (en) * | 2018-01-15 | 2018-05-29 | 杭州臻镭微波技术有限公司 | The radio frequency micro-system and its manufacturing method of a kind of silicon based three-dimensional Manufacturing resource |
| CN108727640A (en) * | 2018-05-31 | 2018-11-02 | 中国科学院苏州纳米技术与纳米仿生研究所 | A kind of Transient Thin-Film, the preparation method of Transient Thin-Film and Transient Thin-Film device |
| CN109285915A (en) * | 2018-08-08 | 2019-01-29 | 西安电子科技大学 | A kind of flexibility transient state silicon thin film phototransistor and production method |
| CN109045063A (en) * | 2018-10-17 | 2018-12-21 | 西北大学 | A kind of injecting temperature sensitive in situ response water soluble chitosan composite hydrogel and its preparation method and application for lacrimal passage embolism |
| CN109528392A (en) * | 2018-10-19 | 2019-03-29 | 浙江大学 | A kind of intelligent antiseptic dressing for infective wound surface perception and therapeutic intervention |
| CN110604566A (en) * | 2019-09-24 | 2019-12-24 | 清华大学 | Flexible deformable degradable brain detection treatment device and system and manufacturing and using methods |
Non-Patent Citations (3)
| Title |
|---|
| Dry Transient Electronic Systems by Use of Materials that Sublime;Bong Hoon Kim;《ADVANCED FUNCTIONAL MATERIALS》;20170324;第1606008（1-8）页 * |
| Modulated degradation of transient electronic devices through multilayer silk fibroin pockets;Brenckle, MA;《ACS Applied Materials and Interfaces》;20150901;第7卷(第36期);第19870-19875页 * |
| 瞬态电子器件研究最新进展;张颖;《中国科学:物理学 力学 天文学》;20160111;第044605（1-9）页 * |
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